Coral diseases: what is really known?

Reports of new and emerging coral diseases have proliferated in recent years. Such coral diseases are often cited as contributing to coral reef decline. Many of these diseases, however, have been described solely on the basis of field characteristics, and in some instances there is disagreement as to whether an observed coral condition is actually a disease. A disease pathogen has been identified for only three coral diseases, and for only two of these has the pathogen been shown (in the laboratory) to be the disease agent. In one case, the same disease name has been used for several widely varying coral syndromes, whereas in another multiple disease names have been applied to symptoms that may be caused by a single disease. Despite the current confusion, rapid progress is being made.     

Chimeric restriction enzymes: what is next?

Chimeric restriction enzymes are a novel class of engineered nucleases in which the non-specific DNA cleavage domain of Fokl (a type IIS restriction endonuclease) is fused to other DNA-binding motifs. The latter include the three common eukaryotic DNA-binding motifs, namely the helix-turn-helix motif, the zinc finger motif and the basic helix-loop-helix protein containing a leucine zipper motif. Such chimeric nucleases have been shown to make specific cuts in vitro very close to the expected recognition sequences. The most important chimeric nucleases are those based on zinc finger DNA-binding proteins because of their modular structure. Recently, one such chimeric nuclease, Zif-QQR-F(N) was shown to find and cleave its target in vivo. This was tested by microinjection of DNA substrates and the enzyme into frog oocytes (Carroll et al., 1999). The injected enzyme made site-specific double-strand breaks in the targets even after assembly of the DNA into chromatin. In addition, this cleavage activated the target molecules for efficient homologous recombination. Since the recognition specificity of zinc fingers can be manipulated experimentally, chimeric nucleases could be engineered so as to target a specific site within a genome. The availability of such engineered chimeric restriction enzymes should make it feasible to do genome engineering, also commonly referred to as gene therapy.     

Statin pharmacogenomics: what have we learned, and what remains unanswered?

PURPOSE OF REVIEW: Statins are widely prescribed and are established as first-line therapy for the primary and secondary prevention of coronary heart disease. Response to treatment varies considerably from person to person; however, inherited traits (genetic variability) may play a central role in this inter-individual variation. The purpose of this review is to summarize recent progress in the research for exploring genetic determinants of clinical efficacy and safety of statin therapy. RECENT FINDINGS: In addition to 41 previous studies of 19 genes, the results of 17 pharmacogenomic studies investigating the relationship between common genetic variants and response to statin therapy in terms of lipid responses, clinical outcomes, and adverse events have been reported since January 2004 - 15 candidate genes related to pharmacodynamics and three to pharmacokinetics of statins. These reported data suggest that genetic variations influencing intestinal cholesterol absorption, cholesterol production, and lipoprotein catabolism may all play a role in modulating responsiveness, as well as genes involved in drug metabolism of statins. They also suggest that combined analysis of multiple variants in several genes, all of which have possible functional relations, is more likely to give significant results, especially when being performed with a larger number of participants. SUMMARY: Pharmacogenomic studies of statin therapy will provide a better picture as to who is most likely and least likely to benefit from treatment, which results in more individualized management of coronary artery disease.     

Selenium intake and cardiovascular risk: what is new?

PURPOSE OF REVIEW: Selenium is an essential element with a narrow safety margin. Adequate selenium intake is needed to maximize the activity of glutathione peroxidases and other selenoproteins. This review discusses recent experimental and epidemiologic contributions on the role of selenium for the prevention of atherosclerotic cardiovascular disease. RECENT FINDINGS: Few randomized trials have evaluated the efficacy of selenium supplementation on cardiovascular endpoints. Most trials, conducted in selenium-replete populations, found no evidence of cardiovascular protection. A meta-analysis of 13 prospective cohort studies found a moderate inverse relationship between plasma/serum selenium and coronary heart disease. The interpretation of these data is complicated, however, by potential residual confounding and publication bias. In contrast, recent data from trials of selenium-containing supplements and from epidemiologic studies suggest that chronically increased selenium intake in selenium-replete populations can induce diabetes and maybe also hypercholesterolemia. SUMMARY: Current evidence is insufficient to support a protective role for selenium in cardiovascular prevention. Large high-quality randomized controlled trials and observational studies are needed across populations with different levels of selenium intake. Furthermore, subjects living in regions with high selenium intake should be aware that selenium supplements may increase their risk of diabetes and hypercholesterolemia.     

Venous ulcer: what is new?

The pathophysiology of venous dermal abnormality in chronic venous ulcers is reflective of a complex interplay that involves sustained venous hypertension, inflammation, changes in the microcirculation, cytokine and matrix metalloproteinase activation, and altered cellular function. Red blood cells and macromolecules extravasate into the interstitium and activate endothelial cells. Endothelial expression of specific adhesion molecules recruits leukocytes and causes diapedesis of these cells into the dermal microvasculature, promoting an inflammatory response with activation of cytokines and proteinases. Altered cell function enhances a state of vulnerability in the surrounding tissues, initiating specific changes associated with venous disease. Ultimately, the persistent inflammatory-proteinase activity leads to advanced chronic venous insufficiency and ulcer formation. The mainstay of therapy in venous ulcer abnormality is correction of the underlying venous hypertension through compression therapy and/or surgery. Understanding the science involved in the pathophysiology of venous ulcer formation has led to the development of adjunctive treatment directed at the dysregulated molecular pathways. Randomized clinical trials are critical for determining the most effective evidence-based treatments for venous ulcer, and this review discusses important trials that have had a significant impact on venous ulcer healing. In addition, the authors have included subsections referred to as "Translational Implications for Therapy" in the basic science sections of the review to help bridge the basic science knowledge with clinical applications that may help to modulate the molecular abnormalities in the pathophysiologic cascade leading to venous ulcers.     

Marine chemical ecology: what''s known and what''s next?

In this review, I summarize recent developments in marine chemical ecology and suggest additional studies that should be especially productive. Direct tests in both the field and laboratory show that secondary metabolites commonly function as defenses against consumers. However, some metabolites also diminish fouling, inhibit competitors or microbial pathogens, and serve as gamete attractants; these alternative functions are less thoroughly investigated. We know little about how consumers perceive secondary metabolites or how ecologically realistic doses of defensive metabolites affect consumer physiology or fitness, as opposed to feeding behavior. Secondary metabolites have direct consequences, but they do not act in isolation from other prey characteristics or from the physical and biological environment in which organisms interact with their natural enemies. This mandates that marine chemical ecology be better integrated into a broader and more complex framework that includes aspects of physiological, population, community, and even ecosystem ecology. Recent advances in this area involve assessing how chemically mediated interactions are affected by physical factors such as flow, desiccation, UV radiation, and nutrient availability, or by biological forces such as the palatability or defenses of neighbors, fouling organisms, or microbial symbionts. Chemical defenses can vary dramatically among geographic regions, habitats, individuals within a local habitat, and within different portions of the same individual. Factors affecting this variance are poorly known, but include physical stresses and induction due to previous attack. Studies are needed to assess which consumers induce prey defenses, how responses vary in environments with differing physical characteristics, and whether the ‘induced’ responses are a direct response to consumer attack or are a defense against microbial pathogens invading via feeding wounds. Although relatively unstudied, ontogenetic shifts in concentrations and types of defenses occur in marine species, and patterns of larval chemical defenses appear to provide insights into the evolution of complex life cycles and of differing modes of development among marine invertebrates. The chemical ecology of marine microbes is vastly underappreciated even though microbes produce metabolites that can have devastating indirect effects on non-target organisms (e.g., red tide related fish kills) and significantly affect entire ecosystems. The natural functions of these metabolites are poorly understood, but they appear to deter both consumers and other microbes. Additionally, marine macro-organisms use metabolites from microbial symbionts to deter consumers, subdue prey, and defend their embryos from pathogens. Microbial chemical ecology offers unlimited possibilities for investigators that develop rigorous and more ecologically relevant approaches.     

Liver diseases: what is known so far about the therapy with human amniotic membrane?

Liver, the largest intern organ of the human body, is responsible for several vital tasks such as digestive and excretory functions, as well as for nutrients storage and metabolic functions, synthesis of new molecules and purification of toxic chemicals. Cirrhosis, fibrosis and hepatocellular carcinoma are the most prevalent liver diseases. Despite all the studies performed so far, treatment options for these diseases are very limited. For this reason, it is urgent to find effective therapies for these pathologies. Several studies have been performed during the last decade about the possible application of human amniotic membrane in hepatic diseases therapy. Promising results about human amniotic membrane or its derived cells, in vitro and in vivo, applications in fibrosis, cirrhosis and hepatocellular carcinoma were already published. Since it is an attractive study area, it is becoming a dynamic scientific subject. However, the action mechanisms of human amniotic membrane and its derived cells in hepatic diseases therapy must be precisely known in order that this promising therapy could be clinically used.     

Genetics of the human metabolome,what is next?

Increases in throughput and decreases in costs have facilitated large scale metabolomics studies, the simultaneous measurement of large numbers of biochemical components in biological samples. Initial large scale studies focused on biomarker discovery for disease or disease progression and helped to understand biochemical pathways underlying disease. The first population-based studies that combined metabolomics and genome wide association studies (mGWAS) have increased our understanding of the (genetic) regulation of biochemical conversions. Measurements of metabolites as intermediate phenotypes are a potentially very powerful approach to uncover how genetic variation affects disease susceptibility and progression. However, we still face many hurdles in the interpretation of mGWAS data. Due to the composite nature of many metabolites, single enzymes may affect the levels of multiple metabolites and, conversely, levels of single metabolites may be affected by multiple enzymes. Here, we will provide a global review of the current status of mGWAS. We will specifically discuss the application of prior biological knowledge present in databases to the interpretation of mGWAS results and discuss the potential of mathematical models. As the technology continuously improves to detect metabolites and to measure genetic variation, it is clear that comprehensive systems biology based approaches are required to further our insight in the association between genes, metabolites and disease. This article is part of a Special Issue entitled: From Genome to Function.     

Immune response in COVID-19: what is next?

The coronavirus disease 2019 (COVID-19) has been a global pandemic for more than 2 years and it still impacts our daily lifestyle and quality in unprecedented ways. A better understanding of immunity and its regulation in response to SARS-CoV-2 infection is urgently needed. Based on the current literature, we review here the various virus mutations and the evolving disease manifestations along with the alterations of immune responses with specific focuses on the innate immune response, neutrophil extracellular traps, humoral immunity, and cellular immunity. Different types of vaccines were compared and analyzed based on their unique properties to elicit specific immunity. Various therapeutic strategies such as antibody, anti-viral medications and inflammation control were discussed. We predict that with the available and continuously emerging new technologies, more powerful vaccines and administration schedules, more effective medications and better public health measures, the COVID-19 pandemic will be under control in the near future. Subject terms: Infectious diseases, Antimicrobial responses     

Marine biodiversity and ecosystem functioning: what's known and what's next?

Marine ecosystems are experiencing rapid and pervasive changes in biodiversity and species composition. Understanding the ecosystem consequences of these changes is critical to effectively managing these systems. Over the last several years, numerous experimental manipulations of species richness have been performed, yet existing quantitative syntheses have focused on a just a subset of processes measured in experiments and, as such, have not summarized the full data available from marine systems. Here, we present the results of a meta‐analysis of 110 marine experiments from 42 studies that manipulated the species richness of organisms across a range of taxa and trophic levels and analysed the consequences for various ecosystem processes (categorised as production, consumption or biogeochemical fluxes). Our results show that, generally, mixtures of species tend to enhance levels of ecosystem function relative to the average component species in monoculture, but have no effect or a negative effect on functioning relative to the ‘highest‐ performing’ species. These results are largely consistent with those from other syntheses, and extend conclusions to ecological functions that are commonly measured in the marine realm (e.g. nutrient release from sediment bioturbation). For experiments that manipulated three or more levels of richness, we attempted to discern the functional form of the biodiversity–ecosystem functioning relationship. We found that, for response variables related to consumption, a power‐function best described the relationship, which is also consistent with previous findings. However, we identified a linear relationship between richness and production. Combined, our results suggest that changes in the number of species will, on average, tend to alter the functioning of marine ecosystems. We outline several research frontiers that will allow us to more fully understand how, why, and when diversity may drive the functioning of marine ecosystems. Synthesis The oceans host an incredible number and variety of species. However, human activities are driving rapid changes in the marine environment. It is imperative we understand ecosystem consequences of any associated loss of species. We summarized data from 110 experiments that manipulated species diversity and evaluated resulting changes to a range of ecosystem responses. We show that losing species, on average, decreases productivity, growth, and a myriad of other processes related to how marine organisms capture and utilize resources. Finally, we suggest that the loss of species may have stronger consequences for some processes than others.     

Phosphatidylserine receptors: what is the new RAGE?

The identification of RAGE as a phophatidylserine receptor—in this issue of EMBO reports by He et al—adds to the range of molecules that can sense this ‘eat-me'' signal, and suggests new potential therapeutic opportunities.EMBO Rep (2011) advance online publication. doi:10.1038/embor.2011.28The recognition of apoptotic cells by phagocytes is a complex, yet highly orchestrated event. Many receptors have been identified that recognize phosphatidylserine (PS; Fig 1)—which is exposed on early apoptotic cells—leading to downstream signalling and apoptotic cell engulfment. In a paper published this month in EMBO reports, the receptor for advanced glycation end-products (RAGE) is described as a new PS receptor on alveolar macrophages that participates in the clearance of apoptotic cells (He et al, 2011).…[RAGE] is described as a new phosphatidylserine receptor on alveolar macrophages that participates in the clearance of apoptotic cellsOpen in a separate windowFigure 1Phosphatidylserine-dependent apoptotic cell recognition.Schematic of the known PS receptors and downstream signalling to Rac. Dashed lines indicate unknown signalling mechanisms. PS, phosphatidylserine; RAGE, receptor for advanced glycation end-products; sRAGE, soluble RAGE.More than 200 billion cells undergo apoptosis every day in a human body, yet few apoptotic cells are detected in healthy tissue (Ravichandran, 2010). Apoptotic cells are generated during development, as part of normal homeostatic turnover and in disease states. The efficient clearance of apoptotic cells is crucial to prevent them from becoming secondarily necrotic, thereby limiting the immune response to apoptotic cell-derived self-antigens (Green et al, 2009). Disruptions to the clearance of apoptotic cells are linked to several diseases including atherosclerosis, chronic inflammation and autoimmunity (Elliott & Ravichandran, 2010).More than 200 billion cells undergo apoptosis every day in a human body, yet few apoptotic cells are detected in healthy tissueApoptotic cell engulfment can be divided into several steps. The first is the release of ‘find-me'' signals—such as triphosphate nucleotides (ATP and UTP), sphingosine-1-phosphate (S1P), lysophosphatidylcholine (LPC) and the chemokine CX₃CL1—by apoptotic cells (Ravichandran, 2010). Then, phagocytes sense the find-me signals and migrate toward the apoptotic cell. When they are in close proximity, recognition is mediated by the interaction between engulfment receptors on phagocytes and ligands, known as ‘eat-me'' signals, that are expressed on the dying cells (Ravichandran, 2010). The best-studied eat-me signal is PS, which is flipped from the inner leaflet to the outer leaflet of the plasma membrane during early apoptosis. Many receptors have been linked to the recognition of the exposed PS on apoptotic cells, and they are discussed below. The recognition of an apoptotic cell results in a downstream signalling cascade that leads to cytoskeletal rearrangement of the phagocytic membrane and subsequent engulfment of the apoptotic cell. Once the corpse is internalized, the phagocyte must process and digest the cellular contents.The exposure of PS on the outer leaflet of the membrane is the most-characteristic marker of an apoptotic cell. Phagocytes can recognize PS directly through receptors such as Bai1, TIM-4 and stabilin 2, or through soluble bridging molecules that bind to both PS and specific phagocyte receptors. For example, bridging molecules MFG-E8 and Gas6 interact with α_Vβ_3/5 and MER on the phagocytic membrane, respectively. Other eat-me signals and the molecules that bind to them have been characterized: thrombospondin is recognized by the vitronectin receptor, calreticulin by LRP1, oxidized LDL by scavenger receptors, ICAM3 might bind to CD14 and altered sugars bind to lectins (Lauber et al, 2004). Not all receptors need to be engaged for engulfment to occur, and different cell types have different receptor-expression levels.In a paper published this month in EMBO reports, the Yamamoto team identify RAGE as a new type of PS receptor on macrophages (He et al, 2011). There are two functional forms of RAGE, an abundant full-length transmembrane form that can initiate signalling through its intracellular tail, and a soluble isoform (sRAGE) that acts as a decoy receptor. RAGE is characteristically regarded as a pro-inflammatory receptor and has a variety of ligands, including advanced glycation end-products (AGEs) and many other damage-associated molecular patterns (DAMPs; Sims et al, 2010). One ligand in particular—high-mobility group protein B1 (HMGB1)—is released by cells undergoing necrosis and has been shown to bind to RAGE and induce inflammation (Sims et al, 2010). Therefore, RAGE might function during pro-inflammatory conditions and—as proposed by He and colleagues—during the anti-inflammatory process of apoptotic cell clearance. RAGE is mainly expressed in the lungs, but levels of it quickly increase at sites of inflammation, mostly on inflammatory and epithelial cells. Given the multitude of RAGE ligands and its inducible expression levels, RAGE is implicated in a variety of inflammation-related pathological states such as neurological and pulmonary disorders, vascular disease, cancer and diabetes (Sims et al, 2010).He and colleagues suggest that RAGE is a PS receptor during apoptotic cell engulfment in alveolar macrophages (He et al, 2011). Furthermore, sRAGE—which can bind to PS and apoptotic thymocytes—acts as a decoy and inhibits RAGE recognition of PS. By using PS liposomes as an artificial apoptotic target, the authors find RAGE in areas of the membrane in which a pseudopod forms to engulf a PS liposome. Additionally, sRAGE can compete with transmembrane RAGE to block the recognition of PS by the phagocyte and subsequently decrease the engulfment of apoptotic cells. Under homeostatic conditions, alveolar macrophages isolated from RAGE-deficient mice have defects in phagocytosis of apoptotic thymocytes. In a model of lung injury induced by lipopolysaccharide administration, RAGE-deficient mice accumulate neutrophils in the alveolar space and RAGE-deficient macrophages have defects in neutrophil engulfment. Previous works have implicated RAGE expression and/or upregulation in inflammatory conditions. In fact, genetic deletion of RAGE in mice can result in attenuated atherosclerosis, resistance to septic shock and reduced diabetic kidney disease (Ramasamy et al, 2010). Apoptotic cell clearance is generally an immunologically silent process and, therefore, if RAGE significantly contributes to engulfment, RAGE-deficient mice would be expected to have defects in cell clearance, leading to enhanced inflammation and disease. However, this does not seem to be the case. Thus, future studies should examine cell-type specific deletions of RAGE to clarify its apparently contradictory role in cell clearance and inflammation in these diseases.Given that several modes of PS recognition have been identified (Ravichandran, 2010), there must be some redundancy. The way in which RAGE contributes to this scenario remains to be investigated. Analysis of the expression levels of each PS receptor on different cell types will also help to define their relative importance in individual cells. As RAGE is highly expressed in the lung, it would be interesting to analyse its contribution to apoptotic cell engulfment in this tissue, in comparison with the other PS receptors. Furthermore, RAGE is induced by inflammation, suggesting that it is probably important during disease states to facilitate engulfment and reduce inflammation in the microenvironment.Another interesting question that remains is how RAGE signals to the phagocyte for engulfment. RAGE signalling results in pro-inflammatory cytokine production through activation of NF-κB (Yan et al, 1994), which seems to be different from the production of anti-inflammatory cytokines—such as IL-10 and TGFβ—by phagocytes during cell engulfment. However, as several RAGE ligands exist, the way in which they bind to RAGE could result in differential signalling. RAGE has also been shown to interact with mouse Dia1, leading to downstream activation of Rac1 and Cdc42, and cell migration (Hudson et al, 2008). Now, He and colleagues suggest that RAGE signals to Rac1 through Dia1 in the context of apoptotic cell clearance, as RAGE-deficient macrophages have decreased Rac1 activity in response to PS-liposome engulfment. Two evolutionarily conserved Rac-dependent pathways have been identified to mediate corpse internalization. Engagement of some engulfment receptors such as Bai1, results in Rac activation through the ELMO–Dock180–CrkII complex. ELMO and Dock180 mediate the exchange of GDP to GTP on Rac, whereas CrkII has been proposed to function as an adaptor protein. Another pathway involves signalling from the engulfment receptor LRP1 or stabilin 2, leading to Rac activation through the engulfment adaptor protein (GULP). Additional work is necessary to determine whether RAGE–mDia1 signalling constitutes a third intracellular signalling pathway for cell engulfment.Another interesting question that remains is how RAGE signals to the phagocyte for engulfmentThe study from the Yamamoto team identifies RAGE as a new PS-recognition molecule implicated in apoptotic cell-clearance in the lung. As each new receptor is identified, we are reminded of the redundancy and cell-type-specific expression of PS receptors. Defects in apoptotic cell-clearance lead to a variety of inflammatory diseases, including cardiovascular and autoimmune diseases. This study could also open an interesting therapeutic avenue; if sRAGE blocks the recognition of PS by RAGE and other PS receptors, it might be beneficial as a therapy by enhancing cell clearance and decreasing the severity of cell-clearance-associated diseases.     

Environmental impacts of food consumption and nutrition: where are we and what is next?

Purpose

This article introduces the special issue “LCA of nutrition and food consumption” and 14 papers selected from the Ninth LCA Food Conference in San Francisco in October 2014.

Literature overview

The scientific literature in the field of food LCA has increased more than ten times during the last 15 years. Nutrition has a high contribution to the total environmental impacts of consumption. Agricultural production often dominates the impacts, but its importance depends on the type of product, its production mode, transport, and processing. Local or domestic products reduce transports, but this advantage can be lost if the impacts of the raw material production are substantially increased. Diets containing less meat tend to be more environmentally friendly. Several studies concluded that respecting the dietary recommendations for a healthy diet would reduce the overall environmental impacts in the developed countries, although this is not a universal conclusion.

Contribution of this special issue

Eight papers analyze the environmental impacts of catering and in-house food consumption and impacts on sectoral and national levels; four papers presents tools and methods to better assess the impacts of nutrition and to implement the results in practical decision-making. Finally, two contributions analyze the impacts of food waste and reduction options.

Challenges for the environmental assessment of nutrition

(i) Comprehensive assessment. Most studies only analyze climate impacts, although data, methods, and tools are readily available for a more comprehensive analysis. (ii) Assessment of sustainability. The social dimension remains the weakest pillar. (iii) Data availability is still an obstacle, but significant progress has been made in recent years. (iv) Lack of harmonization of methodologies makes comparisons among studies difficult. (v) Land use. Enhanced consideration of land use impacts on biodiversity and ecosystem services is required in LCA. (vi) Defining the functional unit including nutritional aspects, food security, and health needs further work. (vii) Consumer behavior. Its impacts are still little assessed. (viii) Communication of the environmental impact assessment results to stakeholders including policy-makers and consumers needs additional efforts.

Research needs and outlook

(i) Development of holistic approaches for the assessment of sustainable food systems, (ii) assessment of land use related impacts and inclusion of ecosystem services, (iii) exploration of LCA results for policy support and decision-making, (iv) investigation of food consumption patterns in developing and emerging countries, and (v) harmonization of databases.

     

Prediction and prevention of schizophrenia: what has been achieved and where to go next?

In modern medicine, vigorous efforts are being made in the prediction and prevention of diseases. Mental disorders are suitable candidates for the application of this program. The currently known neurobiological and psychosocial risk indicators for schizophrenia do not have a predictive power sufficient for selective prevention in asymptomatic patients at risk. However, once predictive basic and later pre-psychotic high risk symptoms of psychosis develop into the five-year initial prodrome, the impending outbreak of the disease can be predicted with high accuracy. Research findings suggest a differential strategy of indicated prevention with cognitive behavioral therapy in early initial prodromal states and low dosage atypical antipsychotics in late initial prodromal states. The most important future tasks are the improvement of the predictive power by risk enrichment and stratification, as well as the confirmation of the existing and the development of new prevention strategies, with a stronger focus on the etiology of the disorder. In addition, the prediction and prevention approach would benefit from the inclusion of risk symptoms in the DSM-5 criteria.     

Adult leukaemia: what is the role of currently known risk factors?

Leukaemias are a heterogeneous group of tumours including acute and chronic forms. Considerable efforts have been made to identify risk factors for these diseases, but only a minority of leukaemia cases can currently be attributed to identified or hypothesized factors. This review highlights recent epidemiological literature concerning adult leukaemia, discussing in detail the hereditary, environmental and medical risks. Chromosomal syndromes and genetically based diseases carry a high risk of leukaemia, but rarely occur in the population. Environmental and occupational exposures to chemicals including pesticides have been widely studied, although the results are not consistent, with the exception of benzene. Smoking seems to be a weak causal risk factor. The risk of ionizing radiation has further been quantified in recent studies, although the effects of low doses have not yet been clarified. The results for non-ionizing radiation continue to be inconsistent, but a large effect of electromagnetic fields on the risk of leukaemia appears to be unlikely. Medically applied radio- and chemotherapy are clearly associated with subsequent leukaemia development, and there are links between leukaemia and viral infections. Future research should emphasize the shortcomings in exposure assessment that pervade many studies, and interactions between different risk factors need to be taken into consideration. Received: 25 September 1997 / Accepted in revised form: 14 October 1997     

Sexual selection and environmental change:what do we know and what comes next?

Anthropogenic environmental change is the most significant threat to biodiversity in the 21st century.Animal populations are experi-encing rapid changes in thei...